Abstract
Serum markers and bone marrow examination are commonly used for monitoring therapy response in multiple myeloma (MM), but this fails to identify minimal residual disease (MRD), which frequently persists after therapy even in complete response patients, and extra-medullary disease escape. Positron emission tomography with computed tomography using 18F-deoxyglucose (FDG-PET/CT) is the reference imaging technique for therapeutic assessment and MRD detection in MM. To date, all large prospective cohort studies of transplant-eligible newly diagnosed MM patients have shown a strong and independent pejorative prognostic impact of not obtaining complete metabolic response by FDG-PET/CT after therapy, especially before maintenance. The FDG-PET/CT and MRD (evaluated by flow cytometry or next-generation sequencing at 10−5 and 10−6 levels, respectively) results are complementary for MRD detection outside and inside the bone marrow. For patients with at least a complete response, to reach double negativity (FDG-PET/CT and MRD) is a predictive surrogate for patient outcome. Homogenization of FDG-PET/CT interpretation after therapy, especially clarification of complete metabolic response definition, is currently underway. FDG-PET/CT does not allow MRD to be evaluated when it is negative at initial workup of symptomatic MM. New PET tracers such as CXCR4 ligands have shown high diagnostic value and could replace FDG in this setting. New sensitive functional magnetic resonance imaging (MRI) techniques such as diffusion-weighted MRI appear to be complementary to FDG-PET/CT for imaging MRD detection. The goal of this review is to examine the feasibility of functional imaging, especially FDG-PET/CT, for therapeutic assessment and MRD detection in MM.
Highlights
Multiple myeloma (MM) is a plasma cell malignancy characterized by a clonal population of bone marrow plasma cells that secrete a monoclonal paraprotein or an immunoglobulin free light chain
Whilst serum markers and bone marrow examination is routinely used for monitoring response to therapy in MM [3], it fails to identify minimal residual disease (MRD), which frequently persists after therapy, even in complete response patients, and extra-medullary disease escape
FDG-PET/CT normalization after three cycles of RVD was observed for 32% of the patients with positive initial imaging, and progression-free survival was significantly enhanced for these patients (30-months progression-free survival, 78.7% vs. 56.8%)
Summary
Multiple myeloma (MM) is a plasma cell malignancy characterized by a clonal population of bone marrow plasma cells that secrete a monoclonal paraprotein or an immunoglobulin free light chain. In 2011, Zamagni et al explored the prognostic relevance of FDG-PET/CT after thalidomidedexamethasone induction therapy and double autologous stem cell transplantation in 192 newly diagnosed MM patients [12] They confirmed the relevance of FDG-PET/CT imaging performed after induction therapy because patients harboring a maximum standardized uptake value (SUVmax, traducing intensity of carbohydrate metabolism) of residual focal bone lesions > 4.2 had a significantly lower progression-free survival. The initial findings of a joint analysis of two independent prospective randomized phase III European trials (Italian and French) were presented by Zamagni and colleagues at the 2018 annual meeting of the American Society of Hematology [17] From this combined analysis of 236 patients, the strongest independent predictor of prolonged progression-free and overall survival was a Deauville score < 4 before maintenance therapy, and was determined using focal bone lesions, bone marrow, and extramedullary disease compared to hepatic background uptake. No prognostic data about CXCR4-directed PET imaging results before or after therapy have been reported yet
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